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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2004-1-28
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pubmed:abstractText |
GB virus B (GBV-B), a flavivirus closely related to HCV, has previously been shown to infect and replicate to high titers in tamarins (Saguinus sp.). This study describes the use of GBV-B infection and replication in the common marmoset (Callithrix jacchus) for the successful development and validation of a surrogate animal model for hepatitis C virus (HCV). Infection of marmosets with GBV-B produced a viremia that peaked at 10(8) to 10(9) genome copies/ml for a period of 40 to 60 days followed by viral clearance at 60 to 80 days postinfection. Passage of the initial tamarin-derived GBV-B in marmosets produced an infectious stock that gave a more reproducible and consistent infection in the marmoset. Titration of the virus stocks in vivo indicated that they contained 1 infectious unit for every 1,000 genome copies. Cultures of primary marmoset hepatocytes were also successfully infected with GBV-B, with high levels of virus detected in supernatants and cells for up to 14 days postinfection. Treatment of GBV-B-infected hepatocyte cultures with a novel class of HCV protease inhibitor (pyrrolidine 5,5 trans-lactams) reduced viral levels by more than 2 logs. Treatment of GBV-B-infected marmosets with one such inhibitor resulted in a 3-log drop in serum viral titer over 4 days of therapy. These studies provide the first demonstration of the in vivo efficacy of a small-molecule inhibitor for HCV in an animal model and illustrate the utility of GBV-B as a surrogate animal model system for HCV.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-10390360,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-10497107,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-10501485,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-10502525,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-10623739,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-10756044,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-10950975,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-11090176,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-11391537,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-11406717,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-11479625,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-11562537,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-11706032,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-11745933,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-11807688,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-12097587,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-12415250,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-12465916,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-12750019,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-12832204,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-4186685,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-4960092,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-4981383,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-7637008,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-7724574,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-8392185,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-8557107,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-9126255,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-9188562,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14747571-9292019
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0022-538X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
78
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2062-71
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:14747571-Animals,
pubmed-meshheading:14747571-Callithrix,
pubmed-meshheading:14747571-Cells, Cultured,
pubmed-meshheading:14747571-Disease Models, Animal,
pubmed-meshheading:14747571-Flaviviridae Infections,
pubmed-meshheading:14747571-GB virus B,
pubmed-meshheading:14747571-Hepatitis, Viral, Animal,
pubmed-meshheading:14747571-Hepatitis C,
pubmed-meshheading:14747571-Hepatocytes,
pubmed-meshheading:14747571-Humans,
pubmed-meshheading:14747571-Protease Inhibitors,
pubmed-meshheading:14747571-Saguinus,
pubmed-meshheading:14747571-Viral Nonstructural Proteins,
pubmed-meshheading:14747571-Virus Replication
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pubmed:year |
2004
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pubmed:articleTitle |
Development of a GB virus B marmoset model and its validation with a novel series of hepatitis C virus NS3 protease inhibitors.
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pubmed:affiliation |
Department of Virology, GlaxoSmithKline Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, United Kingdom. Helen.X.Bright@gsk.com
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pubmed:publicationType |
Journal Article
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